This study proposes to use a non-invasive, in vivo model for strain application in the tibiae of rats. It seeks to examine and compare effects of intermittent parathyroid hormone (PTH) administration and mechanical loading on endosteal bone formation. It hypothesizes that there is a common anabolic pathway for the bone responses to PTH and mechanical loading. It will test three hypotheses with in vivo studies in rats: 1) that PTH modulates the responsiveness of bone tissue to mechanical stimuli; 2) that PTH and mechanical loading modulate osteogenesis through two pathways, i.e., one that includes cell proliferation, one that does not; and 3) that nitric oxide and prostaglandins are common paracrine factors involved in the anabolic effects of mechanical loading and PTH. Bone histomorphometry will be used to measure bone formation rates; immunohistochemistry of bromodeoxyuridine to measure cell division; and serum biochemistry to measure blood chemistry and PTH levels. The proposed studies are intended to lay the groundwork for directed research into the paracrine factors and cellular mechanisms involved in the anabolic response in rat bone. The current studies are directed toward characterization of the cellular events following an anabolic stimulus and the identification of paracrines (nitric oxide and prostaglandins) that may be involved in the anabolic response. Once the cell populations and paracrine factors involved in the anabolic response are identified, further studies may be done to assess cell-to-cell paracrine communication, receptor expression, etc. If PTH shares a common anabolic pathway with mechanical loading, this pathway possibly could be accessed directly, with custom molecules, rather than indirectly using systemic hormones or mechanical loads. It is suggested, therefore, that the proposed research into anabolic bone effects might eventually lead to new therapeutics for treating osteoporosis.